Depression interacts with allostatic load to accelerate cognitive decline, study finds

Depression interacts with allostatic load to accelerate cognitive decline, study finds

New research provides evidence that markers of inflammation, lipid metabolism, and body composition play a key role in predicting the likelihood of cognitive decline among depressed middle-aged adults. The study, published in Psychoneuroendocrinologyfound that history of depression interacted with allostatic load to predict decline in cognitive performance.

Allostatic load is a measure of the cumulative damage that occurs as a result of chronic stress. It includes factors such as high blood pressure and elevated levels of inflammation. Managing allostatic load is critical to maintaining good health. Many studies have shown that high allostatic load is associated with poorer cognitive performance. But this previous work did not assess depression, leaving open questions about the nature of the combined effects of allostatic load and depression on cognition.

“Cognitive changes are common in depression, but the risk of cognitive decline over time is uneven among people with depression,” explained the lead author of the new study, George Perlman from the University of Toronto and the Sunnybrook Research Institute. “We wanted to know what makes some people more at risk. In the field of psychoneuroendocrinology, allostatic load is a kind of ‘theory of everything’ proposed to explain the long-term impact of environmental and psychological stress on overall health.”

“We assessed whether depression, allostatic load, or the two together predicted cognitive decline. We examined people in middle age and followed them for 9 years, because cognitive changes at this time can set the stage for dementia.”

The researchers analyzed data from Midlife in the United States (MIDUS), a national longitudinal study of health and well-being that recruited approximately 7,000 individuals aged 25 to 74 in 1995. The study sought to “investigate the role of behavioral, psychological, and social factors that explain age-related variations in health and well-being in a national sample of Americans.”

Importantly, the study collected a second wave of data between 2004 and 2009 and a third wave of data between 2013 and 2014, which included physiological assessments and cognitive tests. The researchers focused on 815 participants who had depression, physiological, cognitive data. They calculated allostatic load scores based on 24 biomarkers derived from blood samples, urine samples, body measurements and electrocardiographic recordings.

Perlman and colleagues found that depression and allostatic load predicted cognitive decline interactively, but not independently. In other words, high allostatic load was associated with cognitive decline in depressed participants, but not in non-depressed participants.

“People who had both depression and high allostatic load were the most vulnerable to cognitive decline in midlife,” Perlman told PsyPost. “In a sense, depression along with somatic wear and tear on the body ‘added up’ to accelerate cognitive decline.” Future studies looking for ways to preserve cognitive function could focus on those most at risk—ie. individuals who have both depression and high markers of allostatic load such as inflammation and vascular risk factors.”

Cognitive tests included assessment of executive functioning and episodic memory. Examining individual physiological domains, the researchers found that inflammation was the largest moderator.

“Allostatic load is often assessed as a combination of physiological disturbances such as inflammation, metabolic dysfunction, changes in blood pressure, and autonomic dysfunction,” explained Perlman. “When we looked at these components individually, inflammation was the main culprit that, when present alongside depression, predicted a decline in overall cognitive performance.”

None of these physiological disorders predicted episodic memory decline in individuals with or without depression. But the researchers discovered some specific biomarkers that moderated the decline in executive functioning.

“Reductions in brain functions such as speed, information processing, attention, sorting, and general thinking ability (i.e., executive functioning) have been observed particularly in people with allostatic load and depression,” Perlman said. “For executive function decline, lipid metabolism (ie, cholesterol and triglycerides) and body composition (BMI and waist-to-hip ratio) showed the strongest interactions. These metabolic factors are known to be particularly bad for blood vessels.”

“Cognitive outcomes and identified risk factors may indicate vascular dysfunction affecting the brain in depressed individuals. Neuroimaging studies can be useful for examining white matter and regions such as the prefrontal cortex, which are often affected by vascular disease.”

However, as with any study, the results come with some caveats.

“Although the study followed people for 9 years, longer follow-up of larger groups will be needed to determine whether the interactions we found predict incident dementia,” Perlman told PsyPost. “It will also be important to know whether the risk is related to Alzheimer’s disease, vascular dementia or a mixture of the two, which is the most common culprit.”

“The main limitation of this study is demographic; 93% of the study cohort was Caucasian. If we want to know whether these findings generalize to everyone in middle age, this analysis needs to be replicated in non-white populations and those outside of North America.”

“We would like to thank the investigators and staff of the United States Midlife Study for providing the data and for all their friendly guidance throughout,” Perlman added.

The study, “Depression interacts with allostatic load to predict cognitive decline in midlife“, by George Perlman, Hugo Cogo-Moreira, Che-Yuan Wu, Nathan Herrmann and Walter Swardfager.

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